Urogenital Infections and Inflammations

T.E. Bjerklund Johansen, F. M.E. Wagenlehner, Y.-H. Cho, T. Matsumoto, J. N. Krieger, D. Shoskes, K. Naber

Rare cases of urogenital tuberculosis and atypical mycobacterial urogenital infection

 Ekaterina Kulchavenya 1
Svetlana Dubrovina 2
Denis Kholtobin 3
Victor Khomyakov 4
Mete Çek 5


1 Novosibirsk Research TB Institute, Novosibirsk State Medical University, Novosibirsk, Russia
2 Obstetrics and Gynaecology , Rostov Medical State University, Rostov-on-Don, Russia
3 Urology, Novosibirsk TB reseach institute, Novosibirsk, Russia
4 Novosibirsk Research TB Institute, Novosibirsk, Russian Federation
5 Urology, Trakya University, School of Medicine, Edirne, Turkey

Abstract

Tuberculosis is a multisystem disease with myriad presentations and manifestations; it can affect any organ or tissue, excluding only hair and nails. Doctors who are not familiar with extra-pulmonary tuberculosis may not include this disease in their differential diagnostic work-up. The share of urogenital tuberculosis among all extrapulmonary forms gets up to 47%, and it is more often revealed in developing countries.


1 Introduction

World Health Organization (WHO) defines tuberculosis (TB) as a global problem, however, mostly pulmonary TB (PTB) falls under the lights [1]. Urogenital TB (UGTB) doesn’t seem to be a primary concern for WHO, although UGTB is the third-second most common form of extrapulmonary TB. UGTB is an ancient disease and still presents many unsolved problems. Clinical features are flexible and variable; UGTB mimics numerous other diseases in which frequently delays appropriate diagnosis.

We used the following classification of UGTB [2], [3]:

  1. Kidney TB (KTB); KTB is divided into 4 stages, which depend on the level of destruction.
  2. Male genital tuberculosis (MGTB); which includes orchiepididymitis (mono- and bilateral), prostate TB (infiltrative or cavernous forms), TB of seminal vesicles and TB of penis
  3. Female genital tuberculosis (FGTB); when any female genital organ is infected with TB.
  4. Generalized UGTB when both kidneys and genitals are involved.
  5. Urinary tract tuberculosis (UTB) – is always secondary to KTB, includes TB of ureter, bladder TB of 1–4 grades, urethral TB. Complications of KTB/UTB: strictures, fistula, renal failure, arterial hypertension.
  6. Female genital tuberculosis.
  7. Generalized urogenital tuberculosis – simultaneous lesion of urinary organs and genitals; is always considered as complicated.

UGTB is an embodiment of contradictions – from terms and classification till therapy and management. Nevertheless, we have to overcome this quagmire for best understanding this eternal enigmatic and potentially fatal dangerous disease.

The purpose of this study was to discuss the difficulty of timely diagnosis of UGTB because of non-specific clinical picture, atypical course, the wont to hide under the mask of another disease.

2 Material and methods

For literature review we have searched MEDLINE/PubMed with the key words “urogenital tuberculosis”, “rare”, “unusual”. The search for “Urogenital tuberculosis” revealed 7,087 items, “urogenital tuberculosis rare” – 235 items and “urogenital tuberculosis unusual” – 16 items only. Actually most of these issues did not describe exactly rare and unusual cases of urogenital tuberculosis; we selected really unusual and rare cases. Finally, we analyzed the WHO report of 2016, and 57 scientific articles dedicated to unusual features of UGTB.

3 Results

3.1 Urogenital involvement in pulmonary TB patients

Urogenital involvement occurring synchronously with pulmonary tuberculosis (TB), which is frequent in patients with disseminated tuberculosis, may be puzzling. Generalized TB may manifest first with urogenital tuberculosis (UGTB). This scenario was described by Colbert et al. in their case report [4]. The patient presented with vomiting and renal colic. Imaging studies showed nodules throughout the lungs, retroperitoneum, abdominal viscera, and kidneys. Unilateral hydronephrosis was found on renal imaging.

Vulvar TB in a patient with a long history of pulmonary TB was diagnosed as sexually transmitted disease [5]. However, localized papulonecrotic tuberculid of the vulva was diagnosed timely in a 26-year-old Indian woman with lymphatic and pulmonary TB, thanks to a high index of suspicion [6].

3.2 Urogenital TB and cancer

Differential diagnosis of UGTB is very challenging, urogenital carcinoma being one of the most frequent misleading diagnosis. Isolated tuberculous epididymitis (ITE), defined as tuberculous epididymitis without clinical evidence of either renal or prostate involvement, is a rare entity among various clinical presentations of UGTB. Kho and Chan [7] reported a 20-year-old man who presented with a slow-growing painless scrotal mass for 2 months, with the initial workup suspicious for a right para-testicular tumor. Surgical resection of the mass was therefore scheduled. However, severe pain and redness over the patient's right hemi-scrotum were noted on the day of surgery. A repeat scrotal ultrasound revealed findings suggesting a chronic inflammatory process rather than a malignancy. Frozen section of the lesion confirmed the ultrasonographic findings, and the pathology established the diagnosis of ITE [7].

Isolated tuberculous epididymo-orchitis may closely mimic testicular tumour, particularly in patients with no history of systemic TB. A 44-year old man presented with 4 months’ history of left scrotal mass and underwent left orchidectomy following a preliminary diagnosis of testicular tumour. Histopathology revealed testicular tuberculosis [8]. TB orchiepididymitis, in another case was also preliminary misdiagnosed as scrotal tumor [9]. One more patient presented with a scrotal mass in 5 months after the prostate biopsy and was estimated as tumor and managed with unilateral simple orchiepidymectomy. Histopathology revealed TB [10].

Androulaki et al. [11] reported the case of an inflammatory pseudotumor associated with Mycobacterium tuberculosis (Mtb) infection, which was initially mistaken for a renal malignancy both in clinical and radiological settings.

Bouchikhi et al. [12] reported a patient presenting with left back pain associated with urinary frequency and a few macroscopic episodes of hematuria for the past six months. The helical computed tomography revealed a left hydronephrosis and hydroureter secondary to focal wall thickening of the left lumbar ureter. On this basis, authors diagnosed a ureteral tumor. However, a clinical examination showed irritative voiding symptoms as well as epididymitis associated with prostate infection suggesting Mtb assessment of the patient's urine of which the results proved strongly positive [12].

Female genital tuberculosis (FGTB) as well may be a reason for incorrect diagnosis of cancer. Sabita et al. [13] reported a rare case of isolated cervical TB which mimicked carcinoma of the cervix. A 24-year-old woman presented with secondary amenorrhea and post coital bleeding which were present for one year. Vaginal examination revealed a friable cervix which bled with contact. Though the clinical history and the examination findings were suggestive of a cervical malignancy, the histopathological examination revealed a granulomatous TB inflammation [13].

Jaiprakash et al. [14] emphasized that in countries like India, where carcinoma of cervix is very common, cervical TB may easily be mistaken clinically for malignancy. They reported a case of tuberculosis cervicitis (secondary to pulmonary tuberculosis) in a post-menopausal woman, who presented with the complaint of vaginal discharge for a short duration. Vaginal examination showed an ulcerated lesion over anterior the lip of cervix, clinically suggestive of malignancy. However, a Papanicolaou-smear showed features suggestive of TB which was confirmed by biopsy [14].

Massive uterovaginal prolapse with cervical lesion mimicked cervical carcinoma in the case described by Pei Shan Lim et al. [15], and surgery was performed, after histopathology confirmed TB. Vulvar tuberculosis in one case was diagnosed as vulvar carcinoma, and the patient underwent radical surgery, whereupon TB was found by histological investigation [16].

A 61-year-old postmenopausal woman who had undergone surgery and treated with adjuvant chemotherapy for infiltrating ductal carcinoma of the breast five years ago, presented with bloody vaginal discharge, fatigue, weight loss, and low grade fevers at night for two months. Histological examination of the endometrium, done based on the suspicion of a second primary cancer due to the tamoxifen therapy, revealed a granulomatous reaction, Mtb was found by GeneXpert system [17].

3.3 Urolithiasis as a mask and co-morbidity of UGTB

The same clinical features as well as laboratory and X-ray findings in urolithiasis and UGTB may conduce to misdiagnosis these diseases. Wong et al. [18] described a case of UGTB masquerading as a ureteral calculus. Gupta et al. [19] had a patient, who presented with bilateral urolithiasis and features of renal failure; he underwent left nephrectomy after thorough investigations. The biopsy revealed features of KTB. Later the patient underwent right ureteroscopic lithotripsy. Prakash et al. [20] have found confusing picture of extensive renal and ureteral calcification due to TB.

3.4 Bladder tuberculosis

Bladder TB is rather often complication of KTB, but its manifestation may be unusual and misguiding. Kumar et al. [21] reported 2 cases of a TB cavity behind the bladder and prostate which initially eluded diagnosis, and were confirmed only after surgery. Typical for bladder TB situation was reported by Kaneko et al. [22] (2008). A 24-year-old man experienced gross hematuria and dysuria several times a year from the age of 19, presenting to the Urological Department for the first time at age 21, when he was given standard antibiotic treatment for acute cystitis. Although urinary symptoms persisted, he failed to attend for follow-up. He attended another clinic at the age of 24 with increased urinary frequency. Transrectal ultrasonography revealed thickening of the bladder wall, concavity of the right bladder neck, and nodular changes extending from the left bladder neck to the left bladder wall, and Mtb was detected in the urine [22]. For a long time, bladder TB was overlooked – till it became complicated form grade 4.

Bladder TB grade 4 is unsuitable for conservative therapy; cystectomy with following urinary diversion urinary diversion is indicated. There is a risk of development a cancer of neobladder. Lopes et al. [23] presented a case of a 67-year-old patient with a history of augmentation ileocystoplasty 31 years ago because of UGTB. Radiological investigations performed due to asymptomatic microscopic hematuria revealed three contrast-enhancing polyps within the neobladder. The patient underwent enterocystoprostatectomy and histopathological examination of the neobladder revealed mucinous adenocarcinoma in all three polyps, together with a prostatic adenocarcinoma Gleason 7 (3+4) [23].

Spontaneous bladder perforation secondary to TB is very rare, and the diagnosis is often missed. Confirmation of TB via culture takes a long time and starting empirical treatment for TB is necessary. Kong et al. [24] reported a young woman who presented with clinical features of a perforated appendix and was only diagnosed with bladder perforation during laparotomy. She also had distal right ureteral stricture and left infundibular stenosis. The provisional diagnosis of TB was attained via typical histopathological features and a positive Mantoux test. Kumar et al. [25] and Vallejo et al. [26] also described spontaneous bladder rupture secondary to UGTB.

3.5 TB of urethra

Bouchikhi et al. [27] reported an incredible case of UGTB in a man revealed by urethral narrowing and multiple urethro-scrotal fistulas. The patient presented with dysuria, purulent discharge and a meatic penoscrotal fistula. A retrograde and voiding urethrocystography was performed and revealed an extended narrowing of the whole anterior urethra associated with multiple fistulous portions toward the scrotum and perineum. His condition was estimated as nonspecific sclero-inflammatory urethral stricture with complicating fistulas, and patient underwent an urethroplasty. The wound healing was delayed and associated with the persistence of fistulas extending into the corpus cavernosum with purulent discharge. Only now TB was suspected; multiple biopsies were then performed on the periurethral tissue and fistula tracts, and the histological examination confirmed the diagnosis [27]. We suppose in fact in this case there was un-revealed KTB, as TB of urogenital tract is a complication of KTB.

3.6 TB of epididymitis

Rakototiana et al. [28] had met difficulties in diagnosis of isolated testicular tuberculosis in 2 children. The clinical features had no specificity: one case of hydrocele and 1 case of acute scrotal inflammation. Surgical exploration showed testicular nodules in both cases. Only histological examination provided the definitive diagnosis.

A trauma may provoke the exacerbation of the latent TB. The persistent hypertrophy of the right epididymis in young men had been regarded as a sequela of a recent trauma of the scrotum. The diagnosis of tuberculosis was confirmed by epididymal biopsy, by intravenous urography which revealed a cavity in a left superior calix and above all by the presence of Mtb at bacteriological urine examination [29].

3.7 TB of penis

Surprisingly many authors reported on TB of glans penis – and not only as a complication of BCG-therapy for superficial bladder cancer and bladder carcinoma [30].

Cutaneous penile TB in an HIV-positive man masquerading a sexually transmitted infection was confirmed by positive cultures [31]. Toledo-Pastrana et al. [32] reported the case of a patient with ulcerous penile TB, presumably acquired through sexual intercourse. Kar and Kar [33] have found primary TB of penis in a 31 years old male patient who presented with some ulcerated lesions on the glans penis. Diagnosis was established as primary tuberculosis of glans penis, confirmed by biopsy and supported by a strongly positive Mantoux test and positive TB-PCR. There was no co-existing tuberculous infection elsewhere.

Also Sah et al. [34]. (1999) revealed a 60-year-old man presenting with multiple superficial ulcers on the glans penis. Histopathology, a positive tuberculin test result, and therapeutic response to antituberculous therapy confirmed the diagnosis of penile TB. Examination was otherwise normal except for a solitary enlarged reactive lymph node on the right side. And again there was no evidence of coexistent TB infection elsewhere.

Baskin and Mee [35] reported a case of penis TB that presented as a subcutaneous nodule without superficial ulceration as well as Yonemura et al. [36] who have experienced a case of penis TB that appeared as a scab on nodule. A 56-year-old man presented with a 4-month history of a painless subcutaneous nodule at the glans penis. Pathological findings of the nodule showed granulomatous inflammation. Tuberculin tests were strongly positive, but Mtb could not be detected. Savu et al. [37] (2012) presented a case of penile tuberculosis with a bulky penoscrotal formation treated previously for the suspicion of Fournier gangrene.

Karthikeyan et al. [38] described “Water can” penis caused by TB, which was misdiagnosed for a long time. Nakamura et al. [39] discovered 37 cases of TB of penis in Japan in 10 years (between 1978 and 1987).

3.8 Prostate TB

Otherwise isolated prostate TB is more often localization of UGTB. As an example a historical case of a 65-year-old man was described. The patient presented with symptoms of frequency, dysuria and hesitancy, and 10 kg weight loss in the last 6 months, without pulmonary symptoms and negative ELISA test for HIV. Digital rectal examination (DRE) revealed a high volume, irregular and hard prostatic gland. Ultrasound investigation showed a prostatic volume of 39 cm3, without signs of malignancy. Biopsy of the prostatic gland showed multiple granulomas and the Ziehl-Nelsen staining was positive for Mtb [40].

Another case is a 64-year-old man who presented with an obstructive syndrome of the lower urinary tract. After clinical and laboratory examination, prostate cancer was highly suspected. Transrectal biopsy was performed and histological examination showed tuberculous lesions [41].

3.9 Fatal cases of UGTB

Renal TB is difficult to diagnose, because many patients   present themselves with lower urinary symptoms which are typical for bacterial cystitis. Delayed diagnosis may have grave consequences – even fatal. The case of a young woman with renal TB was reported by Daher et al. (2007). The patient was admitted with complaints of adynamia, anorexia, fever, weight loss, dysuria and generalized edema for 10 months. At physical examination she was febrile (39°C), and her abdomen had increased volume and was painful at palpation. Laboratorial tests showed azotemia, leukocytosis, leukocyturia and proteinuria. She was also oliguric. Abdominal echography showed thick and contracted bladder walls and heterogeneous liquid collection in the left pelvic region. Two laparotomies were performed, in which an abscess in the pelvic region was found. Anti-TB treatment with rifampin, isoniazid and pyrazinamide was started. During the follow-up, the urine culture was found to be positive for Mtb. The complex therapy was unsuccessful, and hemodialysis was then started. The computed tomography showed signs of chronic nephropathy, dilated calyces and thinning of renal cortex in both kidneys and severe dilatation of the ureter. The patient developed neurologic symptoms, suggesting TB meningoencephalitis, and died despite of support measures adopted [42].

Dadhwal et al. [43] reported a rare case of TB flare in a 28-year-old nulliparous woman following endometrial aspiration, which drained 30 ml pus. Following this, she developed high-grade fever with pain abdomen, guarding and rigidity. PCR was positive for mycobacterium and histopathology showed necrotizing granulomatous endometritis. She also showed features of FGTB and chronic TB meningitis.

3.10 Tuberculosis of the renal artery as a cause of renovascular arterial hypertension

Bouziane et al. [44] have reported tuberculosis of the renal artery. A 17-year-old patient presenting with renovascular arterial hypertension, was revealed by the ultrasonography, when an occlusion of the right renal artery as well as pararenal and mesenteric polyadenopathy were found. Authors supposed TB etiology of both processes and anti-TB treatment had been carried out. In one month the right renal artery was revascularized with a right iliorenal bypass using reversed internal saphenous vein. The patient was operated with an 18-month follow-up. Arterial pressure was normal without antihypertensive treatment. This case is interesting, but diagnosis was confirmed by good efficiency of anti-TB therapy, not by histology nor bacteriology.

3.11 Granulomatous interstitial nephritis due to tuberculosis

Granulomatous interstitial nephritis (GIN) is an uncommon form of acute interstitial nephritis. Sampathkumar et al. [45] reported the case of a young male who presented with a rapidly progressing renal failure and massive proteinuria. A renal biopsy revealed GIN, and Mtb DNA was found in the biopsy specimen by PCR. The patient was started on anti-TB therapy and steroids besides 11 sessions of hemodialysis.

3.12 Tuberculosis of the uterine cervix

Patients with TB of the uterine cervix were observed by Yang et al., Giacopino et al., Lamba et al. [46], [47], [48]. In our practice as well there were 5 patients with uterine cervix TB, and three of them had sexual partner with prostate TB, and two denied any contact with TB infection.

Singh et al. [49] described two cases of tuberculous cervicitis with variable clinical presentation. In one case, a young woman presented with primary infertility and secondary amenorrhoea. The other is a perimenopausal woman with irregular vaginal bleeding and postcoital blood-stained discharge. The diagnosis was confirmed on histopathological examination of the endocervical curettings and a cervical biopsy.

3.13 Vulva and vagina TB

A 60-year-old woman was admitted to the Department of Obstetrics and Gynecology due to chronic extensive painful genital ulcer. She was treated by antiviral and antifungal regimens but the ulcer persisted. Tissue biopsy was performed then, and acid fast bacilli were found [50].

Nemati et al. [51] also observed a woman that developed vaginal tuberculosis one year after receiving a kidney transplant from a living donor. Her complaints included abdominal pain, fever, and weight loss. Furthermore, her tuberculin skin test was negative.

Sharma et al. [52] reported a case of tubercular vulvar ulcer in a sexually inactive pubertal girl. She had a close contact with active tuberculosis, positive tuberculin skin test, and chronic granulomatous inflammation on vulvar biopsy.

Tiwari et al. [53] reported a case of hypertrophic vulvar tuberculosis of primary origin in a 26-year-old female patient. The diagnosis was mainly based on histopathological examination.

3.14 Overlooked tubo-ovarian tuberculomas

A case of tubo-ovarian tuberculosis mimicking acute appendicitis was described by Akbulut et al. [54]. A 17-year-old woman presented with complaints of right lower quadrant abdominal pain, nausea, and vomiting. Her physical examination findings, ultrasonogram, and leukocyte count were consistent with acute appendicitis. A cystic mass (15 cm × 6 cm) was detected on the right tubo-ovarian structure by laparotomy. The mass was excised while the tubo-ovarian structures were preserved and the need for an appendectomy was avoided. No microbiological evaluation was performed. The histopathological examination of the cystic mass revealed a granuloma with central caseating necrosis surrounded by epithelioid histiocytes [54].

A similar case was presented by Ilmer et al. [55]. A 35-year-old human immunodeficiency virus seropositive woman complained of lower abdominal pain and fever of two days. She underwent surgery due to left adnexal mass suggesting pelvic inflammatory disease. The surgical situs showed four quadrant peritonitis provoked by a tubo-ovarian abscess on the left side. Histopathological evaluation identified a necrotic granulomatous salpingitis and Mtb was identified by PCR.

Exacerbation of latent genital tuberculosis during in vitro fertilisation and pregnancy was described by Huang et al. [56].

3.15 Congenital tuberculosis

The patient of Agrawal et al. [57] was less lucky. They described the case of a male preterm baby who had congenital miliary tuberculosis with multiple intestinal perforations because his mother had widespread destructive pulmonary tuberculosis.

Two cases of congenital TB were reported by Das et al. [58]. The first one was presented at 12 days of age. The mother had been symptomatic for TB in the first trimester but was not diagnosed until her infant developed symptoms. The infant̓s gastric aspirate was acid-fast bacilli (AFB) positive and Mtb-culture positive. PCR on the gastric specimen and mother's sputum demonstrated identical strains. The second baby was presented at 45 days of age and the gastric aspirate was both AFB- and culture-positive. The mother was asymptomatic and contact-tracing of the family failed to detect infection. However, FGTB was found in the mother’s endometrial biopsy [58].

Our own case demonstrates an extremely rare case of TB of placenta in young woman, suffering from genital TB, which was overlooked before delivery. This woman had not known contact with TB infection, had no history of TB, had no complaints before pregnancy and had no special complaints in time of the pregnancy, excluding common ones for this condition. The delivery was in-time with a healthy full-term baby. In the Russian Federation the investigation of the placenta is a standard procedure, and it revealed TB inflammation (Figure 1) and Mtb in the placenta (Figure 2).

Figure 1: TB of placenta. Caseous inflammation, typical for TB.
Figure 1: TB of placenta. Caseous inflammation, typical for TB.
Figure 2: Tissue of placenta, colored by Ziehl-Neelsen stain: Mtb are shown by arrow.
Figure 2: Tissue of placenta, colored by Ziehl-Neelsen stain: Mtb are shown by arrow.

4 Conclusion

Actually UGTB is not a rare disease – but it is an often overlooked disease. The main reasons for delayed diagnostics are two: vague clinical features and a low index of suspicion. We cannot ignore UGTB – late diagnosis mandatory leads to loss of organ. UGTB is an infectious contagious disease, and it is one more reason for its early diagnosis. It is necessary to use all arsenals of bacteriology and histology to confirm UGTB.


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[36] Yonemura S, Fujikawa S, Su JS, Ohnishi T, Arima K, Sugimura Y. Tuberculid of the penis with a scab on the nodule. Int J Urol. 2004 Oct;11(10):931-3. DOI: 10.1111/j.1442-2042.2004.00917.x
[37] Savu C, Surcel C, Mirvald C, Gîngu C, Hortopan M, Sinescu I. Atypical primary tuberculosis mimicking an advanced penile cancer. Can we rely on preoperative assessment? Rom J Morphol Embryol. 2012;53(4):1103-6.
[38] Karthikeyan K, Thappa DM, Shivaswamy KN. "Water can" penis caused by tuberculosis. Sex Transm Infect. 2004 Feb;80(1):75. DOI: 10.1136/sti.2003.007203
[39] Nakamura S, Aoki M, Nakayama K, Kanamori S, Onda S. Penis tuberculid (papulonecrotic tuberculid of the glans penis): treatment with a combination of rifampicin and an extract from tubercle bacilli (T.B. vaccine). J Dermatol. 1989 Apr;16(2):150-3. DOI: 10.1111/j.1346-8138.1989.tb01238.x
[40] López Barón E, Gómez-Arbeláez D, Díaz-Pérez JA. Tuberculosis prostática primaria. Presentación de un caso y revisión de la literatura [Primary prostatic tuberculosis. Case report and bibliographic review]. Arch Esp Urol. 2009 May;62(4):309-13.
[41] Rabesalama SS, Rakoto-Ratsimba HN, Rakototiana AF, Razafimahatratra R, Raherison RA, Rantomalala HY, Randrianjafisamindrakotroka NS. [Isolated prostate tuberculosis. Report of a case in Madagascar]. Prog Urol. 2010 Apr;20(4):314-6. DOI: 10.1016/j.purol.2009.06.004
[42] Daher Ede F, Silva Júnior GB, Damasceno RT, Santos GM, Corsino GA, Silva SL, Gutiérrez-Adrianzén OA. End-stage renal disease due to delayed diagnosis of renal tuberculosis: a fatal case report. Braz J Infect Dis. 2007 Feb;11(1):169-71. DOI: 10.1590/S1413-86702007000100036
[43] Dadhwal V, Gupta N, Bahadur A, Mittal S. Flare-up of genital tuberculosis following endometrial aspiration in a patient of generalized miliary tuberculosis. Arch Gynecol Obstet. 2009 Sep;280(3):503-4. DOI: 10.1007/s00404-009-1082-4
[44] Bouziane Z, Boukhabrine K, Lahlou Z, Benzirar A, el Mahi O, Lekehal B, Mesnaoui A, Bensaid Y. Tuberculosis of the renal artery: a rare cause of renovascular arterial hypertension. Ann Vasc Surg. 2009 Nov-Dec;23(6):786.e7-9. DOI: 10.1016/j.avsg.2008.02.022
[45] Sampathkumar K, Sooraj YS, Mahaldar AR, Ramakrishnan M, Rajappannair A, Nalumakkal SV, Erode E. Granulomatous interstitial nephritis due to tuberculosis-a rare presentation. Saudi J Kidney Dis Transpl. 2009 Sep;20(5):842-5.
[46] Yang CT, Lee YH, Hsu GJ. Tuberculosis of the uterine cervix. Taiwan J Obstet Gynecol. 2012 Sep;51(3):449-51. DOI: 10.1016/j.tjog.2012.07.026
[47] Giacopino D, Colavita D. T.B.C. isolata del collo dell'utero. Sulle difficoltà diagnostiche della lesione tubercolare della cervice uterina: presentazione di due casi [Isolated tuberculosis of the uterine cervix. On the diagnostic difficulties in tuberculous lesions of the uterine cervix: presentation of 2 cases]. Arch Ostet Ginecol. 1968 Jan-Feb;73(1):71-83.
[48] Lamba H, Byrne M, Goldin R, Jenkins C. Tuberculosis of the cervix: case presentation and a review of the literature. Sex Transm Infect. 2002 Feb;78(1):62-3. DOI: 10.1136/sti.78.1.62
[49] Singh S, Gupta V, Modi S, Rana P, Duhan A, Sen R. Tuberculosis of uterine cervix: a report of two cases with variable clinical presentation. Trop Doct. 2010 Apr;40(2):125-6. DOI: 10.1258/td.2009.090423
[50] Buppasiri P, Temtanakitpaisan T, Somboonporn W. Tuberculosis at vulva and vagina. J Med Assoc Thai. 2010 May;93(5):613-5.
[51] Nemati E, Taheri S, Nourbala MH, Einollahi B. Vaginal tuberculosis in an elderly kidney transplant recipient. Saudi J Kidney Dis Transpl. 2009 May;20(3):465-7.
[52] Sharma C, Shekhar S, Sharma V, Sharma M, Aggarwal T. Paucibacillary tubercular vulval ulcer in a sexually inactive pubertal girl: role of therapeutic trial. J Pediatr Adolesc Gynecol. 2012 Dec;25(6):e123-4. DOI: 10.1016/j.jpag.2012.07.005
[53] Tiwari P, Pal DK, Moulik D, Choudhury MK. Hypertrophic tuberculosis of vulva--a rare presentation of tuberculosis. Indian J Tuberc. 2010 Apr;57(2):95-7.
[54] Akbulut S, Arikanoglu Z, Basbug M. Tubercular tubo-ovarian cystic mass mimicking acute appendicitis: a case report. J Med Case Rep. 2011 Aug 10;5:363. DOI: 10.1186/1752-1947-5-363
[55] Ilmer M, Bergauer F, Friese K, Mylonas I. Genital tuberculosis as the cause of tuboovarian abscess in an immunosuppressed patient. Infect Dis Obstet Gynecol. 2009;2009:745060. DOI: 10.1155/2009/745060
[56] Huang HJ, Xiang DR, Sheng JF. Exacerbation of latent genital tuberculosis during in vitro fertilisation and pregnancy. Int J Tuberc Lung Dis. 2009 Jul;13(7):921.
[57] Agrawal RL, Rehman H. Congenital miliary tuberculosis with intestinal perforations. Tuber Lung Dis. 1995 Oct;76(5):468-9. DOI: 10.1016/0962-8479(95)90017-9
[58] Das A, Arora J, Rana T, Porwal C, Kaushik A, Gaur G, Thukral A, Verma S, Kabra SK, Singh UB. Congenital tuberculosis: the value of laboratory investigations in diagnosis. Ann Trop Paediatr. 2008 Jun;28(2):137-41. DOI: 10.1179/146532808X302161

The ZB MED – Information Center for Life Sciences, Germany, together with the European Association of Urology (EAU) provided the opportunity to publish a “Living Textbook” on “Urogenital Infections and Inflammations” in an open access form. This “Living Textbook” represents also an update of the Textbook on Urogenital Infections published 2010 by the International Consultation on Urological Infections and the EAU: http://www.icud.info/urogenitalinfections.html.

The “Living Textbook” will cover infections and inflammations of the kidney, the urinary tract, as well as the male and female genital tract considering pathogenesis, diagnostics, treatment, prophylaxis and future aspects. The “Living Textbook” will be structured into about 26 Sections each with two section co-chairs responsible for peer review of the chapters of each section. Each chapter should reflect the background to the topic and highlight all of the critical evidence relating to the subject. The intention is to provide an up to date, concise synthesis of the literature on that topic, and for clinical topics also recommendations based on levels of evidence for contemporary clinical practice, as well as suggested research recommendations.

The editors hope that this “Living Textbook” may become a useful instrument for physicians of different specialties taking care about patients suffering from these diseases.

Truls E. Bjerklund Johansen (Norway),

Florian ME Wagenlehner (Germany),

Yong-Hyun Cho (South Korea),

Tetsuro Matsumoto (Japan),

John N Krieger (USA),

Daniel Shoskes (USA),

Kurt G. Naber (Germany).

Publishing at PUBLISSO

Your chapter will be published at the PUBLISSO platform (https://books.publisso.de).

Information for corresponding authors

It is necessary for all corresponding authors to register at PUBLISSO.
To register at PUBLISSO please click the following link: http://books.publisso.de/publisso_gold/register

After registration, please complete your user profile. Information from your user profile will appear in the published chapter and the authors board of the book (http://books.publisso.de/publisso_gold/book/52). If you are displayed in the authors board, you can be contacted by readers and other professionals. You can also contact other authors of the book for exchange and to build a network.
(If you do not want to be displayed in the authors board, but stay registered, you can disable this feature in your profile settings. In this case, your affiliation (publication data) will be displayed in the published chapter only.)

We kindly ask you to provide the co-authors email addresses in the manuscript so that we can contact them in case of queries.

Information for co-authors

After publication of your chapter, your affiliation (publication data) will be displayed in the published chapter.

If you also want to be displayed in the authors board of the book (http://books.publisso.de/publisso_gold/book/52), we kindly ask you to register at PUBLISSO. If you are displayed in the authors board, you can be contacted by readers and other professionals. You can also contact other authors of the book for exchange and to build a network.

To register at PUBLISSO please click the following link: http://books.publisso.de/publisso_gold/register

If you do not want to be displayed in the authors board of the book, you do not have to register. Your affiliation (publication data) will be displayed in the published chapter only.

Support

If you have any further questions please don’t hesitate to contact the PUBLISSO editorial office:

E-Mail: livingbooks@zbmed.de
Phone: +49 221 478-7093

General

The textbook will be structured in sections with two co-chairs each. Each section will start with an introductory chapter written by the two respective co-chairs presented like an editorial commentary in regard to the following chapters (see proposed contents of the book). The two co-chairs of each section will also peer review all chapters in their section and stimulate a consensus discussion within their section together with the authors and the main editors if needed.

Chapters

Each chapter should reflect the background to the topic and highlight all of the critical evidence relating to the subject. The intention is to provide an up to date, concise synthesis of the literature on that topic, and for clinical topics also recommendations based on levels of evidence for contemporary clinical practice, as well as suggested research recommendations.

Manuscript

Each manuscript should have up to approximately 3,000 words (excluding abstract, tables/figures and references). The abstract should count about 300 words.

Structure

The outline of each chapter should be structured as follows (similar as in the edition 2010, which can be downloaded for free: http://www.icud.info/urogenitalinfections.html):

  1. Abstract
  2. Summary of recommendations*/key notes*
    (*which ever term is more appropriate)
  3. Introduction
  4. Methods
  5. Results
  6. Further research
  7. Conclusions
  8. Acknowledgement
  9. Conflict of interest of each author
  10. References

Citation style

As a citation style, the Vancouver style is preferred.

Please mark your references in the text with square brackets ([1], [2], ...).

Summary of recommendations

We would like to have the Summary of recommendations at the beginning after the abstract (as in the edition 2010). However, we do not expect as in the edition 2010, that each recommendation is also specified according to Level of Evidence and Grade of Recommendation, because such a claim would not only need a systematic literature search (see below), but also a structured discussion in a defined group of experts.

Systematic literature search

A systematic literature search should be performed, at least of PUBMED/MEDLINE but ideally of several relevant databases in addition (like Cochrane CENTRAL) to find recent, high quality systematic reviews and/or primary research studies. It is not expected to perform for all chapters a de novo systematic review, if such reviews are already published recently, but it still may be indicated for some items. For questions relating therapy, it should be focused on evidence from (systematic reviews of) randomized controlled trials if available.

The method of the systematic literature search needs to be fully described in the section “Methods”, e.g.:

“A systematic literature search was performed for the last ... (usually 10) years in MEDLINE, Cochrane etc. with the following key words ... and the following limitations: e.g. UTI, age (adult?), ... clinical studies ... English ... abstract available ... only peer reviewed ...

A total of ... publications were identified, which were screened by title and abstract ... After exclusion of duplicates ... a total of ... were included into the review (analysis), supplemented by citations or known to the authors ... ”.

Clinical topics

Clinical topics should be focused on the importance to clinical practice according to the up to date scientific knowledge as presented in the literature. It should relate to questions/complaints/symptoms of patient/population concerning definition, diagnosis, therapy/prevention, intervention, and outcome in comparison, if different approaches are feasible. Please choose patient-important outcomes and focus on those, which you deem critical for decision-making.

Level of evidence and grade of recommendations

Any recommendation should be based on the level of evidence and the grade of recommendation. For this purpose the following system, modified from the Oxford Centre for Evidence-based Medicine should be used (EAU guidelines 2015):

Level of evidence (LE)

Level Type of evidence
1a Evidence obtained from meta-analysis of randomised trials
1b Evidence obtained from at least one randomised trial
2a Evidence obtained from one well-designed controlled study without randomization
2b Evidence obtained from at least one other type of well-designed quasi-experimental study
3 Evidence obtained from well-designed non-experimental studies, such as comparative studies, correlation studies and case reports.
4 Evidence obtained from expert committee reports or opinions or clinical experience of respected authorities.

Grade of Recommendations (GoR)

Grade Nature of recommendations
A Based on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomised trial
B Based on well-conducted clinical studies, but without randomised clinical trials
C Made despite the absence of directly applicable clinical studies of good quality

Comments (EAU guidelines 2015)

The aim of assigning a LE and grading recommendations is to provide transparency between the underlying evidence and the recommendation given.

It should be noted that when recommendations are graded, the link between the level of evidence and grade of recommendation is not directly linear. Availability of randomized controlled trials may not necessarily translate into a grade “A” recommendation where there are methodological limitations or disparity in published results.

Alternatively, absence of high level evidence does not necessarily preclude a grade A recommendation, if there is overwhelming clinical experience and consensus. In addition, there may be exceptional situations where corroborating studies cannot be performed, perhaps for ethical or other reasons and in this case unequivocal recommendations are considered helpful for the reader. The quality of the underlying scientific evidence - although a very important factor – has to be balanced against benefits and burdens, values and preferences and costs when a grade is assigned.

Since the same rating system should be used in all chapters, for the sake of brevity the same sentence could be used in “Methods” for all manuscripts, because the rating system will be described in details in the Preface of the book:

“The studies were rated according to the level of evidence and the strength of recommendations graded according to a system used in the EAU guidelines modified from the Oxford Centre for Evidence-based Medicine [1].”

References

[1] European Association of Urology. Guidelines. Methodology section. 2015 ed. Arnhem: European Association of Urology; 2015. p. 3. ISBN/EAN: 978-90-79754-80-9. Available from: http://uroweb.org/wp-content/uploads/EAU-Extended-Guidelines-2015-Edn..pdf

The Living Handbook of Urogenital Infections and Inflammations is issued by:

European Association of Urology
att. Maurice Schlief, EAU executive manager business affairs

P.O.Box 30016
NL-6803 AA Arnhem, The Netherlands

Phone: 0031-26-38.90.680
E-mail: m.schlief@uroweb.org

Editor in Chief

responsible for the contents according to § 5 TMG and § 55 Abs. 2 RStV (Germany):

Kurt G. Naber, MD, PhD
Assoc. Professor of Urology

Technical University of Munich
Karl-Bickleder-Str. 44c
94315 Straubing, Germany

E-mail: kurt.naber@nabers.de

John N. Krieger MD, PhD

University of Washington Section of Urology

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Daniel Shoskes MD, PhD

Cleveland Clinic Glickman Urological and Kidney Institute

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Yong-Hyun Cho MD, PhD

St. Mary's Hospital, The Catholic University of Korea Department of Urology

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Tetsuro Matsumoto MD, PhD

University of Occupational and Environmental Health Department of Urology

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Florian M. E. Wagenlehner MD, PhD

Justus-Liebig University of Giessen Clinic of Urology and Andrology

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Truls Erik Bjerklund Johansen MD, PhD

Oslo University Hospital Urology Department

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Kurt G. Naber MD, PhD

Technical University of Munich

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Riccardo Bartoletti

University of Pisa
Department of Translational Research and New Technologies

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Truls Erik Bjerklund Johansen MD, PhD

Oslo University Hospital
Urology Department

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PD Dr. med. Gernot Bonkat

University Basel
alta uro AG, Merian Iselin Klinik, Center of Biomechanics & Calorimetry (COB)

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Prof. Tommaso Cai MD

Santa Chiara Regional Hospital
Dept. of Urology

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Dr Leyland Chuang

Ng Teng Fong Hospital, National University Health System
Department of Medicine

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Prof. Milan Cizman

University Medical Centre
Department of Infectious Diseases

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Alison Crawford MSc

Queen's University
Department of Psychology

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Pfofessor Svetlana Dubrovina MD, PhD

Rostov Medical State University
Obstetrics and Gynaecology

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Dr Valerie Huei Li Gan MBBS (S'pore), MRCS (Edin), MMed (Surg), FAMS (Urology)

Singapore General Hospital
Department of Urology

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Philip Hanno

University of Pennsylvania

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Ass prof MD Gundela Holmdahl

Queen Silvia Childrens Hospital, Sahlgrens Academy
Pediatric surgery and urology

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Udo B. Hoyme

HELIOS Hospital Erfurt Ltd.
Department of Gynecology and Obstetrics

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David Hunstad

Washington University School of Medicine
Pediatrics / Molecular Microbiology

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Gitte M. Hvistendahl

Aarhus University Hospital

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Prof. Michael KOGAN M.D., PhD

Rostov State Medical University
Department of Urology

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Dr Akihiro Kanematsu

Hyogo College of Medicine
Department of Urology

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Frieder Keller

University Hospital Ulm
Department Internal Medicine 1, Nephrology

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Professor Katarzyna Kilis-Pstrusinska PhD, MD

Wroclaw Medical University
Department of Pediatric Nephrology

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MD, PhD Tae-Hyoung Kim

Chung-Ang University
Urology

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John N. Krieger MD, PhD

University of Washington
Section of Urology

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Prof Ekaterina Kulchavenya

Novosibirsk Research TB Institute, Novosibirsk State Medical University

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Dr Christina Kåbjörn Gustafsson

Ryhov Hospital Jönköping
Pathology

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Dr. Bela Köves

South Pest Teaching Hospital
Department of Urology

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Dr. med. Giuseppe Magistro

Ludwig-Maximilians-University of Munich
Department of Urology

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Vittorio Magri

ASST-North
Urologic Clinic

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András Magyar

South-Pest Hospital
Department of Urology

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Professor Emeritus Brian Morris

University of Sydney
School of Medical Sciences

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Baerbel Muendner-Hensen

ICA-Deutschland e.V.

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Stephen F. Murphy

Feinberg School of Medicine, Northwestern University
Department of Urology

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Kurt G. Naber MD, PhD

Technical University of Munich

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Prof. Yulia Naboka

Rostov State Medical University
Department of Microbiology

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Dr. J. Curtis Nickel MD

Queen's University
Department of Urology

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Professor Ralph Peeker MD PhD

University of Gothenburg
Department of Urology

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Tamara Perepanova

N.A. Lopatkin Research Institute of Urology and Interventional Radiology

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Prof. Gianpaolo Perletti M. Clin. Pharmacol.

University of Insubria
Department of Biotechnology and Life Sciences

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Felice Petraglia

Department of Biomedical, Experimental and Clinical Sciences, University of Florence
Obstetrics and Gynecology

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Dr. Jörgen Quaghebeur PhD. Med. Sci.

University Hospital Antwerp and University Antwerp
Department of Urology

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Yazan F. Rawashdeh

Aarhus University Hospital
Paediatric Urology Section, Department of Urology

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Professor Claus Riedl MD

-
Urology

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Matthew Roberts

The University of Queensland
Faculty of Medicine

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PD Dr. med Guido Schmiemann MPH

Institut für Public Health und Pflegeforschung, Universität Bremen
Abteilung Versorgungsforschung

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Caroline Schneeberger MD PhD

Academic Medical Center (AMC)

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Prof. Dr. med. Peter Schneede

Klinikum Memmingen
Department of Urology

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Aaron C. Shoskes

Des Moines University Medical College of Ostheopathic Medicine

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Daniel Shoskes MD, PhD

Cleveland Clinic
Glickman Urological and Kidney Institute

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Prof. Dr. Roswitha Siener

University of Bonn
University Stone Centre, Department of Urology

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Sofia Sjöström

Queen Silvia Childrens Hospital, Sahlgrens Academy
Pediatric surgery and urology

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Mathew Sorensen

University of Washington School of Medicine
Department of Urology

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Prof. Dr. Dr. Walter Ludwig Strohmaier FEBU

Regiomed-Klinikum Coburg. Medical School Regiomed
Urology and Paediatric Urology

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Satoshi Takahashi

Sapporo Medical University School of Medicine
Department of Infection Control and Laboratory Medicine

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Professor Paul Anantharajah Tambyah

Yong Loo Lin School of Medicine, National University Hospital
Department of Medicine

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Peter Tenke

Jahn Ferenc South Pest Teaching Hospital
Department of Urology

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Praveen Thumbikat


Department of Urology

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Dr. Jose Tiran Saucedo

IMIGO / Universidad de Monterrey
Obstetrics and Gynaecology

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Dominic Tran-Nguyen

Des Moines University

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Dean Tripp

Queen's University
Psychology, Anesthesia & Urology

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Prof. SEONGHEON WIE

The Catholic University of Korea, St. Vincent's Hospital
Division of Infectious Diseases, Department of Internal Medicine

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Florian M. E. Wagenlehner MD, PhD

Justus-Liebig University of Giessen
Clinic of Urology and Andrology

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Assoc. Prof. Christian Wejse

Aarhus University, Aarhus University Hospital
Department of Infectious Diseases/Center for Global Health, Dept of Public Health

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Prof. Dr. Mete Çek

Trakya University, School of Medicine
Urology

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